Historically, CLL has lagged behind the other B-cell malignancies in terms of molecular and biological analysis. This situation is now changing rapidly. We are beginning to make progress in our understanding of the basic biology of CLL. The paradigm of gradual accumulation of apoptotis defective mature B cells is now being replaced by a much more complex and dynamic picture of proliferating CLL stem cells52 continued superantigen drive, and persistent stimulation by a variety of different stromal and perhaps T cells, with constant turnover of cells in the periphery. The nature of the CLL stem cell and the nature of the initiating genetic events in this cell population are key aims; identification of both would hopefully allow the development of more effective and targeted therapies, along the lines of the paradigm established in chronic myeloid leukemia and imatinib.

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